Precise three-dimensional folding of proteins and peptides is important for function. Identification of such biologically active conformations is critical for developing therapeutics based on peptide structures. Geometrically restricted analogs are thus valuable tools, because they reduce energetic costs for folding into binding conformations, and may thereby improve potency, receptor selectivity and metabolic stability.
Synthesis and analysis of constrained peptidomimetics is useful for characterizing the active conformation of biologically relevant peptides. Optimally constrained analogues may exhibit enhanced affinity, because such pre-organized peptides experience less loss of entropy upon receptor binding. In addition, rigid peptide analogues may avoid conformations prone to undesirable effects and exhibit improved pharmacological properties, such as enhanced stability and bioavailability.
The present description refers to a number of documents, the content of which is herein incorporated by reference in their entirety.